title: Hepatocyte apoptosis is enhanced after ischemia/reperfusion in the steatotic liver.
abstract: Liver steatosis is associated with organ dysfunction after hepatic resection and transplantation which may be caused by hepatic ischemia/reperfusion injury. The aim of the current study was to determine the precise mechanism leading to hepatocyte apoptosis after steatotic liver ischemia/reperfusion. Using a murine model of partial hepatic ischemia for 90 min, we examined the levels and pathway of apoptosis, and the peroxynitrite expression, serum alanine aminotransferase levels, and liver histology 1 and 4 h after reperfusion. In the steatotic liver, the peroxynitrite expression increased after ischemia/reperfusion. Significant hepatocyte apoptosis in the steatotic liver was seen after reperfusion, caused by upregulation of cleaved caspases 9 and 3, but not caspase 8. Serum alanine aminotransferase levels were elevated and histological examination revealed severe liver injury in the steatotic liver 4 h after reperfusion. In mice treated with aminoguanidine, ischemia/reperfusion-induced increases in serum alanine aminotransferase levels and apoptosis were significantly reduced in steatotic liver compared with mice treated with phosphate buffered saline. Survival of mice with steatotic livers significantly improved by treatment with aminoguanidine. Our data suggested that the steatotic liver is vulnerable to hepatic ischemia/reperfusion, leading to significant hepatocyte apoptosis by the mitochondrial permeability transition, and thereby resulting in organ dysfunction.
authors.affiliation: Department of General Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana Chuo-ku, Chiba 260-0856, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Katsunori
authors.initials: K
authors.lastname: Furukawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: Ayako
authors.initials: A
authors.lastname: Iida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Dochi
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki